Beta Fulltext view is in preview — article structure may vary. Browse all articles
Contents
Medical Journal of Clinical Trials & Case Studies Research Article 11 min read

Methylphenidate - Appraisement of Clinical Indications and Contraindications

Bianca CV, Maria Clara MM, Stefanye CM and Mirto NP*
* Corresponding author
ISSN: 2578-4838  10.23880/mjccs-16000262  Received: August 28, 2020  Published: October 06, 2020
 — views
 48 references
 1 table
PDF
Keywords
Methylphenidate Amphetamine Attention deficit hyperactivity disorder Psychological Subtypes Mild
Abstract

Introduction: The prescription of methylphenidate still generates controversies regarding the safety and risk. Objectives: To discuss the current use of methylphenidate, being under medical supervision or not. Methods: For this literature review, scientific articles were used as a basis, from sites such as SCIELO, PUBMED in the English and Portuguese languages, from the 1990s to the year 2020. Conclusions: Although some risks with their ingestion are reported, these end up not exceeding the benefits that the drug can provide in the treatment of people are reported with attention deficit and hyperactivity disorder.

Introduction

The questions involved in the administration of methylphenidate still generate controversies regarding the safety and risk of its consumption. The possibility of side effects, as well as the inability to guarantee the expected results is not decisive factors in preventing consumption, which indicates that the universality of risk performance is consistent with current values [1].

We intended to discuss the current use of methylphenidate, being under medical supervision or not. The possible side effects and benefits of using this famous medicine are analyzed.

Methodology

For this literature review, scientific articles were used as a basis, from sites such as SCIELO, PUBMED in the English and Portuguese languages, from the 1990s to the year 2020.

Clinics

Methylphenidate increases the dopaminergic signal by blocking dopamine transporters. Its acute form reduces the intrinsic functional connectivity between the thalamus and the prefrontal lateral cortex based on regional differences and the expression of dopamine transport.

Methylphenidate is an amphetamine derivative, having been used in the 1950s to treat chronic fatigue and narcolepsy [2]. At that time, its use was not related to psychiatric syndromes. It was manly employed for weight loss, improving athletic performance and as self-medication to improve intellectual activities [3]. Its effects begin from 20 to 60 minutes after injection, with a peak of action around 2 hours lasting from three to five hours [4].

Methylphenidate pharmacokinetics: after oral administration its active substance (methylphenidate hydrochloride) is rapidly and almost completely absorbed.

Intake with food has no relevant effects on absorption. Biotransformation occurs through the fast and extensive carboxylesterase CES1A1. Methylphenidate is eliminated from the plasma with a half-life of 2 hours. After oral administration, 78 to 97% of the dose is excreted in the urine and 1 to 3% in the feces via metabolites [4].

In Brazil, according to the ordinance updated by ANVISA resolution 18/2003, the drug is described as a psychotropic substance of international control, subject to a special notification type, which signals it as a narcotic “substance that can determine physical or psychological dependence listed as such in the lists approved by the Single Convention on Narcotic Drugs [5].

Like any kind of medication, methylphenidate does not bring only benefits, as it can cause risks to the patient’s health depending on its dose and time of use. Some effects can be seen, not as dependent on the medication, but on the underlying disease. Clinical complaints such as anxiety, sadness and stare are reported. The most frequent effects related to the use of the drug are insomnia and loss of appetite [6].

Table with the main side effects caused by methylphenidate: Frequency of the appearance of fallouts in patients using methylphenidate with low dose (0,3 mg/kg), high dose (0,5 mg/kg) and placebo.

PlaceboLow doseHigh dose
Reduction of apetite155256
Insomnia406268
Abdominal pain183935
Headache112621
Propensity of cry495954
Twitcher181828
Giddiness4107
Anxiety585852

Table 1: Table with the main side effects caused by methylphenidate.

Modificated of Barkley RA, MC Murray MB, Edelbrock CS, et al. Side effects methylphenidate in children with attention deficit hyperactivity disorder a systemic placebo-controlled evaluation pediatrics 1990 86(2): 184-192. Systemic effects are assed in several studies. It is mentioned that its abusive use leads to shots of apoptotic cascades, which can cause brain deficiency. In its therapeutic application, this drug reduces motor restlessness, improves status of concentration, attention and memory [7, 8, 9, 10]. In relation to the central nervous system, it increases the state of wakefulness, reduces fatigue, raises the state of mind and promotes a slight euphoria [11].

Its main application is focused on people with attention deficit hyperactivity disorder (ADHD) [12]. The disorder was first described as a transient and childhood disorder, which did not reach adolescence. However, studies have shown that ADHD is currently described as a psychiatric disorder that can last for the entire life of the patient, requiring continuous treatment [13].

The psychiatric diagnosis of ADHD is very common in childhood [14]. As many as 3 to 5% of children in school age presented this diagnosis [15, 16, 17]. Males have more incidence of ADHD: 1.5 boys to 1 girl. However, a considerable difference is noticed when comparing sex with the demand for care in child psychiatric outpatient clinics. In this case, the rate of 9 boys to 1 girl cane can observed. It is admitted that this discrepancy is due to the more aggressive behavior related to the male gender [17, 18, 19, 20, 21]. Treatment with methylphenidate in ADHD has been associated with improvement in two executive functions, related to the prefrontal cortex, and memory deficits dependent on hippocampal activity [10, 11, 14, 16, 17, 18, 19, 20, 22, 23, 24, 25, 26]. Most scientific publications, which address ADHD, confirm the existence of advantages in using methylphenidate, which is considered indispensable while treating this disorder. It has been confirmed that the use of methylphenidate causes a remission of the symptoms of ADHD, improvement in academic and academic performance, good tolerance to medication and its “anti-addiction” effect by reducing the risks of drug abuse in youth [19, 27].

Discussion

Methylphenidate was synthesized by the Swiss Leandro Panizzon and gradually began to be commercialized in several countries as a psychostimulant [28]. Ritalin (commercial form of methylphenidate) in the 1950s was mainly indicated for elderly people to improve fatigue [3]. In the year 1960, psychiatrist Leon Eisenberg published a study on the use of methylphenidate in learning disorders, as soon as it began to be understood that psychostimulants can reduce agitation in the so-called agitated children [29].

The third edition of the American Psychiatric Society book (DSM-III- 1980) considered the diagnosis of attention deficit as a psychiatric category with this new description, methylphenidate has increasingly reached the first-line treatment space. When the fourth edition of the book (DSM- IV) was launched in 1994, the diagnosis of attention deficit was changed to attention deficit hyperactivity disorder [23, 29]. Three subtypes were described: the predominantly inattentive, the predominantly hyperactive and the combined [23]. The fifth edition (DSM-V -2013) established criteria for the diagnosis of ADHD in adults with the subtypes mild, moderate and severe. Currently, one evident increase in use was observed for the purpose of improving cognitive performance, with satisfactory results [30]. Ritalin is also used improperly by young people in order to reduce hunger, residual fatigue and to enhance physical and mental performance [1]. Currently, the sale of this medication is illegal, without a medical prescription, which helps to harm the health of many people in our country [31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48].

Conclusions

Since methylphenidate was synthesized, its use has increased until reaching the place of the most widely used psychostimulant in the world. Although there are risks with their ingestion, these end up not exceeding the benefits that the drug can provide in the treatment of people with attention deficit and hyperactivity disorder The widest problem related to this drug is the indiscriminate use, which can lead people without any medical indication to acquire drug dependence, with serious damage to their physical and mental health.

References

  1. Adam XG, Tiffany RL, Nicholas B, Salvatore Ti, Bari F, et al. (2020) Intrinsic connections between thalamic sub-regions and the lateral prefrontal cortex are differentially impacted by acute methylphenidate. Psychopharmacology 237: 1873-1883.
  2. Paulo Mattos (2013) Entenda o TDAH nos critérios do DSM-5. ABDA.
  3. (2003) Agência nacional de vigilância sanitária – ANVISA. RDC 18(28).
  4. Andreazza AC, Frey BN, Valvassori SS, Zanotto C, Gomes KM, et al. (2007) DNA damage in rats after treatment with methylphenidate. Prog Neuro Psychopharmacol Biol Psychiatry 31(6): 1282-1288.
  5. Barkley RA, Mcmurray MB, Edelbrock CS, Robbins K (1990) Side Effects of Methylphenidate in Children with Attention Deficit Hyperactivity Disorder: A Systemic Placebo-controlled Evaluation. Pediatrics 86(2): 184- 192.
  6. Bedard AC, Tannock R (2008) Anxiety, methylphenidate response, and working memory in children with ADHD. J Atten Disord 11(5): 546-557.
  7. Bethancourt JA, Camarena ZZ, Britton GB (2009) Exposure to oral methylphenidate from adolescence through young adulthood produces transient effects on hippocampal sensitive memory in rats. Behav Brain Res 202(1): 50-57.
  8. Biederman J (1998) Attention-Deficit/Hyperactivity Disorder: a life-span perspective. J Clin Psychiatry 59: 14-16.
  9. (2010) BPR. Guia de Remédios – edição. 10th (Edn.), São Paulo: Escala.
  10. Dupanloup A (2004) L’Hyperactivité Infantile: Analyse Sociologique d’une Controverse Socio-Médicale. Tese de Doutorado em Ciências Sociais, Université de Neuchâtel, Switzerland, pp: 1-371.
  11. Gonçalves, Cristina de S, Pedro, Maria Rosa RL (2018) Drogas da Inteligência?”: Cartografando as controvérsias do consumo da Ritalina para o aprimoramento cognitivo – Psicol Conoc Soc 8(2): 53-67.
  12. Itaborahy C (2009) A ritalina no Brasil: uma década de produção, divulgação e consumo. Dissertação (Mestrado) – Instituto de Medicina Social, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, pp: 1-126.
  13. Joffe V (2005) Um dia na vida de um adulto com TDAH. São Paulo: Lemos Editorial.
  14. Mattos P (2005) No mundo da lua: perguntas e respostas sobre transtorno do déficit de atenção com hiperatividade em crianças,adolescentes e adultos. São Paulo: Lemos Editorial.
  15. Conrad P, Potter D (2000) From hyperactive children to ADHD adults: observations on the expansion of medical categories. Soc Probl 47(4): 559-582.
  16. Weiss M, Murray C (2003) Assessment and management of attention-deficit hyperactivity disorder in adults. CMAJ 168(6): 715-722.
  17. Korolkovas A (2006) Dicionário terapêutico Guanabara. 13th (Edn.), Rio de Janeiro: Guanabara Koogan.
  18. Kramer AF, Cepeda NJ, Cepeda ML (2001) Methylphenidate effects on task-switching performance in attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 40(11): 1277-1284.
  19. Kwasman A, Tinsley BJ, Lepper HS (1995) Pediatricians’ knowledge and attitudes concerning diagnosis and treatment of attention deficit and hyperactivity disorders. Arch Pediatr Adolesc Med 149(11): 1211- 1216.
  20. Motaghinejad M, Motevalian M, Shabab B, Fatima S (2017) Effects of acute doses of methylphenidate on inflammation and oxidative stress in isolated hippocampus and cerebral cortex of adult rats. J Neural Transm 124(1): 121-131.
  21. Pereira CSC (2009) Conversas e Controvérsias: uma análise da constituição do TDAH no cenário científico e educacional brasileiro. Dissertação de Mestrado, Programa de Pós-graduação em História das Ciências e da Saúde, Casa de Oswaldo Cruz/Fiocruz, Rio de Janeiro.
  22. (2008) PR Vade-Mécum de medicamentos. 14th (Edn. ) São Paulo: Soriak.
  23. Richters JE, Arnold LE, Jensen PS, Howard A, Keith Conners, et al. (1995) NIMH collaborative multisite multimodal treatment study of children with ADHD: I. Background and rationale. J Am Acad Child Adolesc Psychiatry 34(8): 987-1000.
  24. Rhodes SM, Coghill DR, Matthews K (2006) Acute neuropsychological effects of methylphenidate in stimulant drug-naïve boys with ADHD II - broader executive and non-executive domains. J Child Psychol Psychiatry 47(11): 1184-1194.
  25. Scahill L, Schwab-Stone M (2000) Epidemiology of Adhd in school-age children. Child Adolesc Psychiatr Clin N Am 9(3): 541-555.
  26. Singh I (2007) Not just naughty: 50 years of stimulant drug advertising. In: A Toon, Watkins E (Eds.), Medicating Modern America, New York: New York University Press, pp: 131-155.
  27. Stubbe DE (2000) Attention-deficit/hyperactivity disorder: an overview and historical perspective, current controversies, and future directions. Child Adolesc Psychiatr Clin N Am 9(3): 469-479.
  28. Sunohara GA, Malone MA, Rovet J, Humphries T, Roberts W, et al. (1999) Effect of methylphenidate on attention in children with attention deficit hyperactivity disorder (ADHD): ERP evidence. Neuropsychopharmacology 21: 218-228.
  29. Taylor E (1994) Syndrome of attention deficit and overactivity. In: Rutter M, Taylor E, Hersov L (Eds.) Child and adolescent psychiatry modern approaches, 3rd (Edn.), Osney Mead: Blackwell, pp: 285-307.
  30. Tófoli D (2006) País vive febre da ‘droga da obediência’. Folha de São Paulo, São Paulo, Caderno Cotidiano, pp: C1.
  31. Mattos P (2005) No mundo da lua: perguntas e respostas sobre transtorno do déficit de atenção com hiperatividade em crianças, adolescentes e adultos. São Paulo: Lemos Editorial.
  32. Pastura G, Mattos P (2004) Efeitos colaterais do metilfenidato. Rev Psiquiatr Clin 31(2): 100-104.
  33. Verster JC, Bekker EM, Kooij JJ, Buitelaar JK, Verbatenet MN, al. (2010) Methylphenidate significantly improves declarative memory functioning of adults with ADHD. Psychopharmacology (Berl) 212: 277-281.
  34. RL’histoire de Ritalin W (1999) Un Workshop à Lucerne a fait voir ce classique sous un nouveau jour. Stimulants dans la psychiatrie de l’adulte (prof. Brigitte Woggon). Lucerne (Switzerland): Life Sci 2: 8-9.
  35. Wilens TE, Biederman J (1992) The stimulants. Pediatric Psychopharmacol 15(1): 191-22.
  36. Spencer T, Biderman J, Wilens T, Margaret H, O’donnell D, et al. (1996) Pharmacotherapy of attention-deficit hyperactivity disorder across the life cycle. J Am Acad Child Adolesc Psychiatry 35(4): 409-432.
  37. Swanson JM, McBurnett K, Christian DL, Wigal T (1995) Stimulant medications and the treatment of children with ADHD. Advance in Clinical Child Psychology 17: 265-322.
  38. Swanson JM, McBurnett K, Wigal T, Pfiffner LJ, Lerner MA, et al. (1993) Effect of stimulant medication on children with attention deficit disorder: A ”Review of reviews”. Exceptional Children 60(2): 154-162.
  39. Greenhill LI, Halperin JM, Abikofe H (1999) Stimulant medications. Am J Acad Child Adolesc Psychiatry 38(5): 503-512.
  40. Wang R, Qin J, Liu X (2003) Clinical and sleep EEG monitoring characteristics and long-term follow-up study on narcolepsy. Chin J Pediatr 41(1): 11-13.
  41. Francisco GE, Ivanhoe CB (1996) Successful treatment of post-traumatic narcolepsy with methylphenidate. A case reports. Am J Phys Med Rehabil 75(1): 63-65.
  42. Mitler MM, Shafor R, Hajdukovich R, Timms RM, Browman CP (1986) Treatment of narcolepsy: objective studies on methylphenidate, pemoline and protriptyline. Sleep 9(1): 260-264.
  43. Honda Y, Hishikawa Y, Takahashi Y (1979) Long- term treatment of narcolepsy with methyphenidate (Ritalin®). Current Ther Res 26(2): 288-298.
  44. Daly DD, Yoss RE (1956) The treatment of narcolepsy with methyl phenylpiperidylacetate: a preliminary report. Staff Meetings of the Mayo Clinic 31(23): 620- 626.
  45. Yoss RE, Daly D (1959) Treatment of narcolepsy with Ritalin. Neurology 9(3): 171-173.
  46. Protocol 07 (2000) A multicenter, double-blind, randomized, placebo-controlled, parallel-group, evaluation of the safety and efficacy of a modified-release oral dosage form of methylphenidate-HCl (Ritalin-QD) in children with ADHD. Novartis Pharmaceuticals Corp., East Hanover, USA.
  47. Ritalin LA [Clinical Overview] for adult ADHD patients. Novartis. Ritalin LA [Summary of Clinical Efficacy] for adult ADHD patients. Novartis.
  48. Ritalin LA (2013) Clinical Overview of long-term safety and efficacy in attention-deficit/hyperactivity disorder in adults. Novartis.
More from this journal

Cite this article

BibTeX
APA
RIS
@article{bianca2020,
  title   = {Methylphenidate - Appraisement of Clinical Indications and Contraindications},
  author  = {Bianca CV, Maria Clara MM, Stefanye CM and Mirto NP},
  journal = {Medical Journal of Clinical Trials & Case Studies},
  year    = {2020},
  volume  = {4},
  number  = {4},
  doi     = {10.23880/mjccs-16000262}
}
Bianca CV, Maria Clara MM, Stefanye CM and Mirto NP (2020). Methylphenidate - Appraisement of Clinical Indications and Contraindications. Medical Journal of Clinical Trials & Case Studies, 4(4). https://doi.org/10.23880/mjccs-16000262
TY  - JOUR
TI  - Methylphenidate - Appraisement of Clinical Indications and Contraindications
AU  - Bianca CV, Maria Clara MM, Stefanye CM and Mirto NP
JO  - Medical Journal of Clinical Trials & Case Studies
PY  - 2020
VL  - 4
IS  - 4
DO  - 10.23880/mjccs-16000262
ER  -